Total parenteral nutrition (TPN) has gained acceptance as a feeding technique for achieving positive nitrogen balance, weight gain and enhanced wound healing in patients who are unable to tolerate oral nutrition. The development of hepatic steatosis is a metabolic complication associated with TPN that is difficult to detect early and is poorly understood; this problem is often serious in critically-ill or chornically-dependent patients who cannot tolerate interruption of life-sustaining TPN. The purpose of the experiments proposed here is to examine the nutritional basis, metabolic changes and methods for detecting fatty liver metamorphosis in an intravenously-fed rat model. The first specific aim is to determine the contribution that energy-yielding nutrients made to hepatic fat accumulation during TPN. To fulfill this aim, rats will receive intravenous infusates containing varying quantities of carbohydrate and lipid calories, and hepatic lipid content will be measured. From these data, the combinations and levels of non-protein kilocalories producing minimum and maximum fat accumulation will be identified. The second specific aim is to describe metabolic alterations that contribute to the accumulation of fat in the liver of intravenously-fed rats. In this regard, the lipogenic potential of the liver will be assessed by quantifying hepatic enzyme activities that support lipogenesis and by determining the rate of incorporation of 3H20 into livers lipids in vivo. Also, fatty acid oxidation, esterification and lipoprotein formation in isolated hepatocytes will be studied in rats receiving infusates that minimize and maximize hepatic lipid content. Finally, the third specific aim is to identify a non-invasive technique that detects fatty liver infiltration during TPN. To fulfill this objective, externally detectable, lipophilic radiopharmaceuticals will be administered to rats with TPN-induced steatosis to determine if hepatic retention of these substances correlates with liver lipid content. The information obtained during the course of these studies will be directed toward the long-term objective of normalizing hepatic lipid metabolism in patients requiring TPN. Identification of a non-invasive test suitable for detecting hepatic steatosis in humans will facilitate the process of formulating TPN infusates that maintain hepatic integrity in human subjects.